POS0964 IS LOW VERTEBRAL BONE DENSITY ASSOCIATED WITH SUBSEQUENT BONE FORMATION AT THE SAME VERTEBRA IN AXIAL SPONDYLOARTHRITIS? – A MULTILEVEL ANALYSIS FROM THE SIAS COHORT
Authors: M. L. Marques, N. Pereira Da Silva, D. Van der Heijde, R. Stal, X. Baraliakos, J. Braun, M. Reijnierse, C. Bastiaenen, F. A. Van Gaalen, S. Ramiro
Journal: Annals of the Rheumatic Diseases (2022)

Background In radiographic axial spondyloarthritis (r-axSpA) it has been hypothesized that inflammation-driven bone loss triggers bone repair at anatomically distinct sites of the same vertebra: bone loss occurring in the trabecular bone and ectopic bone formation in the periosteum 1 . Objectives To investigate whether inflammation is associated with lower bone density (surrogate of bone loss) and subsequently, if lower bone density is associated with 2-year bone formation in r-axSpA at the same vertebra. Methods Data from the Sensitive Imaging in Ankylosing Spondylitis (SIAS), a multicentre 2-year cohort, was used. Baseline vertebral bone density was assessed by Hounsfield Units (HU) on low dose Computed Tomography (ldCT) by two independent readers (Figure 1). Baseline magnetic resonance imaging (MRI) bone marrow edema (BME) status scores, and 2-year ldCT syndesmophyte formation or growth change scores were assessed by three and two readers respectively. Inter-reader reliability was assessed for each imaging scoring by vertebra. Average of readers´ continuous scores (bone density HU) or readers´ agreement in binary scores (MRI-BME and bone formation) were used at the same vertebra (1-present in ≥1 quadrant/0-absent in all quadrants). The hypothesised associations were tested in multilevel generalised estimating equations models adjusted for confounders, the unit of analysis being the vertebra. Results We analysed 1,100 vertebrae in 50 patients with r-axSpA. Intraclass correlation coefficients for HU measurements varied from 0.89 to 0.97, Fleiss Kappa values for MRI-BME were between 0.41-0.78 and Cohen´s kappa for syndesmophyte formation/growth change scores varied from 0.36 to 0.74. Bone density HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at the thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant association was found between inflammation (MRI-BME) and lower bone density (regression coefficient=-51; 95% CI:-63;-39) (Table 1 A ). Bone density was not associated with 2-year syndesmophyte formation or growth (adjOR 1.00; 95% CI:0.99;1.00) (Table 1 B ). Table 1. Relationships between (A) baseline MRI detected spinal inflammation (MRI-BME) and bone density, and (B) baseline bone density and ldCT bone formation after two years, at the same vertebra. A. Independent variables Bone density (Hounsfield Units ) Univariable analysis Multivariable analysis Reg coeff. (95% CI) Adj Reg coeff. (95% CI) N = 910 to 985 N = 985 MRI-BME (presence) -51 (-63 to -39 ) -51 (-63 to -39 ) Age (years) -1 (-2 to 1) -1 (-2 to 1) Gender (male) 21 (-20 to 63) 16 (-24 to 57) TNFi treatment (yes) 26 (-7 to 59) 27 (-6 to 61) Baseline syndesmophytes (presence)* -42 (-54 to -30 ) - B. Independent variables Syndesmophyte formation or growth§ Univariable analysis Multivariable analysis OR (95% CI) AdjOR (95% CI) N = 672 to 691 N = 672 Bone density (HU) 1.00 (0.99 to 1.00) 1.00 (0.99 to 1.00) Age (years) 1.02 (0.99 to 1.06) 1.02 (0.98 to 1.05) Gender (male) 0.44 (0.13 to 1.52) 0.56 (0.15 to 2.06) Smoking (current) 0.89 (0.40 to 1.97) 1.02 (0.42 to 2.44) Treatment with TNFi (yes) 1.34 (0.56 to 3.21) 1.30 (0.43 to 3.90) MRI-BME (presence) 2.03 (1.23 to 3.71 ) 1.73 (1.06 to 3.34 ) Baseline syndesmophytes (presence)* 2.84 (1.83 to 4.41 ) - *Multicollinearity with MRI-BME. § Absolute agreement of readers. adjOR - adjusted odds ratio; CI -confidence interval; BME - bone marrow edema; HU - Hounsfield units; ldCT - low dose computed tomography; MRI - magnetic resonance imaging; TNFi – Tumour necrosis factor inhibitors. Statistical significance highlighted in bold. Conclusion While in r-axSpA vertebral inflammation associates with low vertebral bone density, lower vertebral bone density itself does not increase the risk for ectopic bone formation at the same vertebra. References [1]Lories RJ. Best Pract Res Clin Rheumatol. 2018 Jun;32(3):331–41. Acknowledgements To the Dutch Rheumatism Association for funding SIAS study. Disclosure of Interests Mary Lucy Marques: None declared, Nuno Pereira da Silva: None declared, Désirée van der Heijde Consultant of: AbbVie, Gilead, Glaxo-Smith-Kline, Lilly, Novartis, UCB Pharma, Rosalinde Stal: None declared, Xenofon Baraliakos: None declared, Juergen Braun: None declared, Monique Reijnierse: None declared, Caroline Bastiaenen: None declared, Floris A. van Gaalen: None declared, Sofia Ramiro: None declared